When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in many tissues, their dysfunction being associated with cancer and ciliopathies, a diverse group of congenital human diseases. Several recent studies have unveiled functional connections between primary cilia and NRF2 (nuclear factor erythroid 2-related factor 2), the master transcription factor orchestrating cytoprotective responses to oxidative and other cellular stresses. These NRF2-cilia relationships are reciprocal: primary cilia, by promoting autophagy, downregulate NRF2 activity. In turn, NRF2 transcriptionally regulates genes involved in ciliogenesis and Hedgehog (Hh) signaling, a cilia-dependent pathway with major roles in embryogenesis, stem cell function and tumorigenesis. Nevertheless, while we found that NRF2 stimulates ciliogenesis and Hh signaling, a more recent study reported that NRF2 negatively affects these processes. Herein, we review the available evidence linking NRF2 to primary cilia, suggest possible explanations to reconcile seemingly contradictory data, and discuss what the emerging interplay between primary cilia and NRF2 may mean for human health and disease.

中文翻译：

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NRF2和主要纤毛：新兴伙伴关系。

当不分裂时，许多细胞类型会将其中心体靶向质膜，在质膜中成核初级纤毛的成核，初级纤毛是一种由九个同心微管对组成的天线状信号结构，被膜包围。原发纤毛在许多组织中起着重要的病理生理作用，它们的功能障碍与癌症和纤毛病（多种先天性人类疾病）有关。最近的几项研究揭示了初级纤毛和NRF2（核因子红系2相关因子2）之间的功能联系，NRF2是协调对氧化应激和其他细胞应激的细胞保护反应的主要转录因子。这些NRF2-纤毛关系是相互的：初级纤毛通过促进自噬而下调NRF2活性。反过来，NRF2转录调节参与纤毛和刺猬（Hh）信号传导的基因，纤毛依赖性途径在胚胎发生，干细胞功能和肿瘤发生中起主要作用。尽管如此，尽管我们发现NRF2刺激纤毛生成和Hh信号传导，但最近的一项研究报道NRF2会对这些过程产生负面影响。在这里，我们审查了将NRF2与原发纤毛联系起来的现有证据，提出了调和看似矛盾的数据的可能解释，并讨论了原纤毛和NRF2之间出现的相互作用对人类健康和疾病的意义。最近的一项研究报道，NRF2对这些过程有负面影响。在这里，我们审查了将NRF2与原发纤毛联系起来的现有证据，提出了调和看似矛盾的数据的可能解释，并讨论了原纤毛和NRF2之间出现的相互作用对人类健康和疾病的意义。最近的一项研究报道，NRF2对这些过程有负面影响。在这里，我们审查了将NRF2与原发纤毛联系起来的现有证据，提出调和看似矛盾的数据的可能解释，并讨论了原发纤毛和NRF2之间出现的相互作用对人类健康和疾病的意义。